Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Hippocampus. 2014 Mar;24(3):326-40. doi: 10.1002/hipo.22226. Epub 2013 Nov 26.
The parvalbumin (PV)-positive neurons in the medial septum-diagonal band of Broca complex (MS-DB) play an important role in the generation of hippocampal theta rhythm involved in cognitive functions. These neurons in this region express a high density of 5-HT1A receptors which regulate the neuronal activity and consequently affect the theta rhythm. In this study, we examined changes in the theta-related firing activity of PV-positive neurons in the MS-DB, their response to 5-HT1A receptor stimulation and the corresponding hippocampal theta rhythm, and the density of PV-positive neurons and their co-localization with 5-HT1A receptors in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The lesion of the SNc decreased the rhythmically bursting activity of PV-positive neurons and the peak frequency of hippocampal theta rhythm. Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.5-128 µg/kg, i.v.) inhibited the firing rate of PV-positive neurons and disrupted rhythmically bursting activity of the neurons and the theta rhythm in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition and disruption in the lesioned rats were higher than that of sham-operated rats. Furthermore, local application of 8-OH-DPAT (0.005 μg) in the MS-DB also inhibited the firing rate of PV-positive neurons and disrupted their rhythmically bursting activity in sham-operated rats, while having no effect on PV-positive neurons in the lesioned rats. The lesion of the SNc decreased the density of PV-positive neurons in the MS-DB, and percentage of PV-positive neurons expressing 5-HT1A receptors. These results indicate that the lesion of the SNc leads to suppression of PV-positive neurons in the MS-DB and hippocampal theta rhythm. Furthermore, the lesion decreases the response of these neurons to 5-HT1A receptor stimulation, which attributes to dysfunction and/or down-regulation of 5-HT1A receptor expression on these neurons. These changes may be involved in cognitive impairments of Parkinson's disease.
脑桥旁正中复合体中（MS-DB）的颗粒蛋白（PV）阳性神经元在涉及认知功能的海马体θ节律产生中发挥重要作用。该区域的这些神经元表达高密度的 5-HT1A 受体，调节神经元活动，从而影响θ节律。在这项研究中，我们检查了 MS-DB 中 PV 阳性神经元的与θ相关的放电活动、它们对 5-HT1A 受体刺激的反应以及相应的海马体θ节律的变化，以及黑质致密部（SNc）中 6-羟多巴胺损伤大鼠中 PV 阳性神经元的密度及其与 5-HT1A 受体的共定位。SNc 的损伤降低了 PV 阳性神经元的节律性爆发活动和海马体θ节律的峰值频率。全身性给予 5-HT1A 受体激动剂 8-羟基二丙胺（8-OH-DPAT，0.5-128μg/kg，iv.）抑制了 PV 阳性神经元的放电率，并分别破坏了 sham 操作和损伤大鼠的神经元节律性爆发活动和θ节律。在损伤大鼠中产生抑制和破坏的累积剂量高于 sham 操作大鼠。此外，MS-DB 中局部应用 8-OH-DPAT（0.005μg）也抑制了 sham 操作大鼠中 PV 阳性神经元的放电率，并破坏了它们的节律性爆发活动，而对损伤大鼠中的 PV 阳性神经元没有影响。SNc 的损伤降低了 MS-DB 中 PV 阳性神经元的密度和表达 5-HT1A 受体的 PV 阳性神经元的百分比。这些结果表明，SNc 的损伤导致 MS-DB 中 PV 阳性神经元和海马体θ节律的抑制。此外，损伤降低了这些神经元对 5-HT1A 受体刺激的反应，这归因于这些神经元上 5-HT1A 受体表达的功能障碍和/或下调。这些变化可能与帕金森病的认知障碍有关。
